National Research Council of Canada. Human Health Therapeutics
Immunology 2014 Meeting Abstracts, May 2-6, 2014, Pittsburgh, Pennsylvania
Leukocyte recruitment towards sites of infection involves coordinated ligand-receptor interactions between leukocytes and the vascular wall. Selectins transiently bind to selectin ligands to enable leukocyte tethering and rolling on the vascular wall prior to leukocyte adhesion and transmigration into tissues. These interactions occur following post-translational modifications of selectin ligands, including terminal fucosylation by Fucosyltransferase-IV and -VII. In mice, deficiency in both enzymes (FtDKO) leads to loss of leukocyte tethering and rolling, increased circulating neutrophils and impaired T cell trafficking. However, the role of functional selectin ligand interactions in modulating immunity to bacterial infections remains unclear. We analyzed the kinetics of infection and modulation of immune responses in FtDKO mice infected with Listeria monocytogenes, an intracellular bacterium. FtDKO mice controlled systemic infection more rapidly relative to wild-type mice. This was correlated to increased number and functionality of neutrophils. Adoptive transfer of bone marrow cells from FtDKO mice into irradiated wild-type mice resulted in expansion of neutrophil populations and increased resistance to infection in a neutrophil-dependent manner. Functional selectin ligand deficiency on neutrophils was correlated to increased resistance to cell death. Thus, functional selectin ligand expression is a potential target for enhancing innate immunity against bacterial infection.
American Association of Immunologists
The Journal of Immunology192, no. 1_Supplement (1 May 2014).